Arsenic trioxide induces apoptosis in NB-4, an acute promyelocytic leukemia cell line, through up-regulation of p73 via suppression of nuclear factor kappa B-mediated inhibition of p73 transcription and prevention of NF-kappa B-mediated induction of XIAP, cIAP2, BCL-X(L) and survivin

作者：Momeny Majid; Zakidizaji Majid; Ghasemi Reza; Dehpour Ahmad R; Balaei Maryam Rahimi; Abdolazimi Yassan; Ghavamzadeh Ardeshir; Alimoghaddam Kamran; Ghaffari Seyed H^*

来源：Medical Oncology, 2010, 27(3): 833-842.

DOI：10.1007/s12032-009-9294-9

• Arsenic trioxide
• p73
• Nuclear factor kappa B
• Acute promyelocytic leukemia

The purpose of the present study is to evaluate the effects of arsenic trioxide (ATO) on human acute promyelocytic leukemia NB-4 cells. Microculture tetrazolium test, bromodeoxyuridine (BrdU) cell proliferation assay, caspase 3 activity assay, cell-based nuclear factor kappa B (NF-kappa B) phosphorylation measurement by ELISA and real-time RT-PCR were employed to appraise the effects of ATO on metabolic activity, DNA synthesis, induction of programmed cell death and NF-kappa B activation. The suppressive effects of ATO on metabolic potential, cell proliferation and NF-kappa B activation were associated with induction of apoptosis in NB-4 cells. In addition, an expressive enhancement in mRNA levels of p73, cyclin-dependent kinase inhibitor 1A (p21), tumor protein 53-induced nuclear protein 1 (TP53INP1), WNK lysine deficient protein kinase 2 (WNK2) and lipocalin 2 coupled with a significant reduction in transcriptional levels of NF-kappa B inhibitor beta (IKK2), Nemo, BCL2-like 1 (BCL-X(L)), inhibitor of apoptosis protein 1 (cIAP2), X-linked inhibitor of apoptosis protein (XIAP), survivin, Bcl-2, TIP60, ataxia telangiectasia (ATM), SHP-2 and sirtuin (SIRT1) were observed. Altogether, these issues show for the first time that ATO treatment could trammel cell growth and proliferation as well as induces apoptosis in NB-4 cells through induction of transcriptional levels of p73, TP53INP1, WNK2, lipocalin 2 as well as suppression of NF-kappa B-mediated induction of BCL-X(L), cIAP2, XIAP and survivin. Furthermore, the inductionary effects of ATO on transcriptional stimulation of p73 might be through cramping the NF-kappa B module (through suppression of p65 phosphorylation as well as transcriptional hindering of IKK2, ATM and Nemo) along with diminishing the mRNA expression of TIP60, SHP-2 and SIRT1.

• 出版日期2010-9